title: Translational control of Nrf2 within the open reading frame.
abstract: Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) is a transcription factor that is essential for the regulation of an effective antioxidant and detoxifying response. The regulation of its activity can occur at transcription, translation and post-translational levels. Evidence suggests that under environmental stress conditions, new synthesis of Nrf2 is required - a process that is regulated by translational control and is not fully understood. Here we described the identification of a novel molecular process that under basal conditions strongly represses the translation of Nrf2 within the open reading frame (ORF). This mechanism is dependent on the mRNA sequence within the 3' portion of the ORF of Nrf2 but not in the encoded amino acid sequence. The Nrf2 translational repression can be reversed with the use of synonymous codon substitutions. This discovery suggests an additional layer of control to explain the reason for the low Nrf2 concentration under quiescent state.
authors.affiliation: Department of Biochemistry and Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA, USA. operez@temple.edu
authors.forename: Oscar
authors.initials: O
authors.lastname: Perez-Leal
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Barrero
authors.forename: Salim
authors.initials: S
authors.lastname: Merali
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D001483:Base Sequence; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation / Q000235:genetics; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D016366:Open Reading Frames / Q000235:genetics*; D014176:Protein Biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D000596:Amino Acids; D051267:NF-E2-Related Factor 2; D012333:RNA, Messenger
keywords: Nrf2; Oxidative stress; Translational control